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Endocrinology Flashcards

1
Q

What are the three groups of hormone?

A

Protein/peptide
Steroid
Miscellaneous

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2
Q

What are peptide hormones initially produced as? Give an example.

A

Inactive prohormones

E.g. ACTH is produced as pro-opiomelanocortin (POMC)

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3
Q

Describe the synthesis of protein/peptide hormones.

A

Amino acids are delivered to the cell. These are used to synthesise the peptide hormones in the same way that all proteins are synthesised. Genome –> mRNA –> protein

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4
Q

What are all steroid hormones derived from?

A

Cholesterol

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5
Q

How is cholesterol stored in cells and what do they look like in the cell?

A

Cholesterol is delivered in LDLs and then it is stored as fatty acid esters, which appear as fatty droplets in the cell. Steroid producing cells have a lot of fat droplets.

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6
Q

Where are most steroid hormones produced?

A

Adrenals and gonads

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7
Q

What enzyme breaks down fatty acid esters?

A

Esterase

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8
Q

Where does steroid hormone synthesis take place within the cell?

A

Mitochondrion

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9
Q

How does cholesterol get into the mitochondrion?

A

Via StAR proteins (steroidogenic acute regulatory proteins)

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10
Q

As all steroid hormones are derived from cholesterol, what determines the final hormone produced?

A

The combination of enzymes that are found within the cell

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11
Q

In terms of secretion, how are steroid hormones and peptide hormones different?

A

Steroid hormones are secreted immediately into the blood (as they are produced). Peptide hormones are packaged into vesicles and remain by the cell surface awaiting a signal before they are exocytosed.

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12
Q

State some key features of protein/polypeptide hormones and state how they are stored.

A

Protein/polypeptide hormones are stored in the cells that produce them. They have a short half life.

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13
Q

How are steroid hormones transported/stored?

A

They are transported in the blood - bound to carrier proteins such as albumin or other specific carriers such as cortisol and corticosteroid binding globulin.

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14
Q

State two ways in which the steroid hormone equilibrium in the blood can be shifted.

A

Uptake of steroid hormones by tissue - leads to the release of some of the protein bound hormone to re-establish previous free steroid hormone levels.
Rise in plasma protein levels - more plasma proteins means that you are more likely that the plasma proteins will bind to the hormone so more protein bound hormone is formed.

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15
Q

Give two examples of how the steroid hormone equilibrium can be shifted.

A

Cortisol is a stress hormone and in times of stress, more of the free cortisol enters the tissues so the free cortisol levels fall.
In pregnancy more plasma proteins are synthesised.

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16
Q

Describe the mechanism of action of ACTH in stimulating cortisol production.

A

ACTH receptors are usually G-protein coupled receptors.
Binding of ACTH to the receptor activates adenylate cyclase, which converts ATP to cAMP. The increase in cAMP activates Protein Kinase A. Esterase is phosphorylated, and so cholesterol is liberated. Phosphorylation of the StAR protein activates the StAR protein allowing cholesterol to move into the mitochondrion. This then stimulates steroid hormone production

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17
Q

What type of receptor do steroid hormones bind to?

A

Intracellular receptors - they act as transcription factors

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18
Q

Describe the feedback loop of ACTH and cortisol.

A

The anterior pituitary is stimulated by stress and ACTH is released. ACTH acts on the adrenal gland to increase cortisol production. Cortisol returns to the anterior pituitary and switches off cortisol production.

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19
Q

What is the bony shelf that the pituitary is found in?

A

Sella Turcica

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20
Q

Describe the embryological origin of the pituitary gland.

A

The adenohypophysis originates from glandular tissue from the buccal cavity that extends upwards and fuses with an extension of neural tissue from the developing hypothalamus that forms the neurohypophysis. Eventually the connection to the buccal cavity is cut off.

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21
Q

Which ventricle is the hypothalamus located near?

A

3rd ventricle

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22
Q

What are the two areas of the brain that are useful anatomical markers for distinguishing the posterior pituitary from the anterior?

A

Anterior - optic chiasma

Posterior - mammilary body

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23
Q

What are hypothalamic nuclei?

A

They are groups of neuronal cell bodies that can be grouped functionally.

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24
Q

Where is the median eminence?

A

It is located between the pituitary stalk and the hypothalamus.

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25
Describe the blood supply in the pituitary gland.
The primary capillary plexus is found in the median eminence. It is connected, via the hypothalamo-hypophysial portal system to the secondary capillary plexus in the adenohypophysis. The blood from the secondary capillary plexus drains via the cavernous sinus and out via the jugular veins. NOTE: primary capillary plexus comes from the superior hypophysial artery
26
What is a key feature of the primary capillary plexus?
The capillary is fenestrated (there are small holes in it)
27
Describe how the hypothalamus exerts control over the adenohypophysis.
Some neurones from the hypothalamus terminate on the median eminence at the primary capillary plexus. The neurosecretions released by these neurones are hormones that travel via the hypothalamo-hypophysial system to the secondary capillary plexus where they stimulate the secretion of adenohypophysial hormones.
28
What are the FIVE types of adenohypophysial cells and what hormones do they produce?
``` Somatotrophs - somatotrophin Lactotrophs - prolactin Gonadotrophs - LH and FSH Thyrotrophs - Thyrotrophin Corticotrophs - corticotrophin (ACTH) ```
29
What are the THREE types of adenohypophysial hormone? Give examples of each.
Protein - somatotrophin + prolactin Glycoprotein - FSH + LH + thyrotrophin Polypeptide - ACTH NOTE: Glycoproteins have an alpha chain and a beta chain. They all have the same alpha chain but have different beta chains.
30
State the EIGHT hypothalamic hormones and the adenohypophysial hormones that they control.
Somatotrophin releasing hormone + somatostatin = somatotrophin Dopamine + Thyrotrophin releasing hormone = prolactin Gonadotrophin releasing hormone + gonadotrophin inhibitory hormone = FSH + LH Thyrotrophin releasing hormone = thyrotrophin Corticotrophin releasing hormone + vasopressin = corticotrophin
31
State the tissues that the FIVE adenohypophysial hormones act on.
``` Somatotrophs - most cell (hepatocytes in particular) Prolactin - breasts in lactating women Gonadotrophin - gonads Thyrotrophin - thyroid Corticotrophin - adrenal cortex ```
32
Describe the two modes of action of somatotrophin.
Somatotrophin can act directly on tissues by binding to somatotrophin receptors or it can act on hepatocytes and stimulate hepatocytes to produce IGF 1, which is particularly important in growth
33
What are the metabolic actions of somatotrophin?
Somatotrophin stimulates amino acid transport into cells, stimulates protein synthesis, increases cartilaginous growth, stimulates lipid metabolism leading to increased fatty acid production and decreased glucose utilisation resulting in increased blood glucose concentration.
34
What has a negative feedback effect on somatotrophin?
Somatotrophin itself and somatomedins have a negative feedback effect on somatotrophin production.
35
What stimulates somatotrophin release?
Sleep, stress, oestrogens, exercise, fasting (hypoglycaemia), amino acids
36
What is the main effect of prolactin?
Prolactin stimulated lactogenesis in the breast.
37
What are some other effects of prolactin?
Prolactin is also a natural contraceptive as it inhibits LH release. It also upregulates LH receptors in the gonads. It decreases sexual behaviour and has effects on the immune system.
38
Describe the neuroendocrine reflex of prolactin.
There are tactile receptors in the nipple that are stimulated by the suckling of the baby and has an afferent pathway to the hypothalamus and stimulates the release of thyrotrophin releasing hormone and inhibits dopaminergic neurones. Prolactin starts the synthesis of milk for the next suckling period.
39
What is a hypothalamic nucleus?
A collection of cell bodies that send their axons to a particular place.
40
State the two main hypothalamic nuclei.
Supraoptic | Paraventricular
41
What is the other hypothalamic nucleus where the biological clock resides?
Suprachiasmatic
42
What two molecules are produced by the neurohypophysis?
Vasopressin | Oxytocin
43
What are the two types of neurone and how do they differ?
``` Parvocellular: Average sized Terminate in the median eminence and other parts of the brain ONLY from paraventricular nucleus Magnocellular: LARGE Terminate in neurohypophysis Nuclei in both paraventricular AND supraoptic nuclei ```
44
Describe supraoptic neurones.
They are ALL MAGNOCELLULAR and terminate in the neurohypophysis They are either oxytocinergic or vasopressinergic. The neurosecretions are hormones because they release directly into the circulation.
45
What is a key feature of magnocellular neurones?
Herring Bodies - areas where neurosecretions can be stored on their way down to the neurohypophysis
46
Describe the synthesis of Vasopressin. What other molecules are produced when the prohormone is cleaved?
``` Vasopressin is synthesised from Pre-provasopressin Cleaved to produce: Arginine vasopressin Glycopeptide Neurophysin ```
47
Describe the synthesis of Oxytocin.
``` Synthesised from pre-prooxytocin Cleaved to produce: Oxytocin Neurophysin (different to that produced from pre-provasopressin) Does NOT produced glycopeptide ```
48
State the main differences between Arginine Vasopressin and Oxytocin.
AVP has PHENYLALANINE instead of ISOLEUCINE | AVP has ARGININE instead of LEUCINE
49
State some similarities between Arginine Vasopressin and Oxytocin.
They are both nonapeptides They are both synthesised from prohormones Prohormones are cleaved to produce neurophysin
50
What is the main effect of vasopressin?
Increased water reabsorption in the kidney collecting ducts
51
What are some other effects of vasopressin?
Vasoconstriction Synthesis of blood clotting factors Corticotrophin release Hepatic glycogenolysis
52
What are the different types of vasopressin receptor and which cells express these receptors?
``` V1a MOST IMPORTANT Vasculature Brain V1b Involved in control of corticotrophin release Adenohypophysial cells (corticotrophs) V2 Involved in antidiuretic effect Kidney collecting duct cells ```
53
Describe how V1 and V2 receptors work.
``` V1 = Gq protein linked receptor (PLC; PIP2 ---> IP3 + DAG; increase in [Ca2+]) V2 = Gs protein linked receptor (adenylate cyclase; increase cAMP; PKA) ```
54
Explain how vasopressin acts on cells in the kidney collecting duct.
AVP binds to V2 on collecting duct cells Activates adenylate cyclase ---> increase in cAMP ----> activate PKA ---> increased synthesis of AQUAPORIN 2 AQP2 ---> assembled into aggraphores ---> aggraphores migrate to apical membrane ---> water moves in ---> water moves out of cell down concentration gradient via AQP3 + AQP4
55
What are the two main functions of vasopressin and how is vasopressin release stimulated?
``` Water Reabsorption Vasoconstriction Stimuli: Increase in plasma osmolality Fall in blood pressure ```
56
What are the two main actions of oxytocin?
Oxytocin is a CONTRACTOR molecule. Main actions: Contraction of the myometrial cells during CHILDBIRTH MILK EJECTION - contraction of myoepithelial cells in the breast during lactation
57
What are the two main functions of vasopressin and how is vasopressin release stimulated?
``` Water Reabsorption Vasoconstriction Stimuli: Increase in plasma osmolality Fall in blood pressure ```
58
What are the two main actions of oxytocin?
Oxytocin is a CONTRACTOR molecule. Main actions: Contraction of the myometrial cells during CHILDBIRTH MILK EJECTION - contraction of myoepithelial cells in the breast during lactation
59
Explain these two actions of oxytocin.
Oxytocin is release in massive amounts during delivery It acts on the myometrial cells to cause contraction Prolactin stimulates milk PRODUCTION but NOT milk ejection Oxytocin stimulates the contractile myoepithelial cells around the ducts and alveoli to cause MILK EJECTION
60
What is a stimulus for oxytocin release when breastfeeding?
Stimulation of tactile receptors around the nipple passes message via a neuroendocrine reflex arc to the neurohypophysis and stimulates oxytocinergic neurons, resulting in oxytocin release. NOTE: this is a different neuroendocrine arc to the one that stimulates release of prolactin from the adenohypophysis
61
State two conditions associated with vasopressin.
SIADH - too much ADH produced, decreases plasma osmolality, increases urine concentration Diabetes Insipidus - characterised by polydypsia and polyuria, in central diabetes insipidus - NO VASOPRESSIN produced

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